Many pulmonary toxins exert discrete and localized reations within the lungs suggesting that the heterogeneous population of lung cells vary considerably with respect to interactions with xenobiotics. In order to elucidate the differential effects of various toxins on the lung cell populations, techniques for isolating and characterizing the major cell-types from a number of animal species are being developed. The cell-types of principal interest include the vascular endothelial cells, alveolar type I and type II cells, and the interstitial fibroblasts and pericytes which constitute over 90% of the lung mass. Further, the bronchiolar Clara cells and alveolar macrophages are also of interest because of their known metabolic activities. Isolation and identification of capillary endothelial cells were undertaken because these cells rapidly undergo morphological changes following treatment of animals with several pulmonary toxins such as high oxygen tensions, monocostaline and Alpha-naphthylthiourea. Rabbit lung cells were dispersed into single cell suspensions and subjected to centrifugal elutriation. Various cell fractions were collected at increasing flow rates and the presence of endothelial cells was detected by measuring angiotensin converting enzyme (ACE) and 5-hydroxytryptamine metabolism. The endothelial cells were enriched in the first fraction removed from the elutriator indicating that the size of this cell population is small compared to other pneumocytes. Further enrichment was achieved by subjecting the first elutriator fraction to a noncontinuous percoll density gradient. The cell fraction at the 0-20% percoll interface contained the highest ACE activity and represented a 3-5 fold enrichment of the cells. Studies are presently under way to characterize this cell population by both light and electron microscopy.